Attenuation of gastric mucosal inflammation induced by aspirin through activation of A_(2A) adenosin

来源 :World Journal of Gastroenterology | 被引量 : 0次 | 上传用户:JK0803_lichunfeng
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AIM:To determine whether a specific adenosine A_(2A) re-ceptor agonist(ATL-146e)can ameliorate aspirin-inducedgastric mucosal lesions in rats,and reduce neutrophil ac-cumulation and production of pro-inflammatory cytokines.METHODS:Gastric lesions were produced by oralgarage of aspirin(200 mg/kg)and HCl(0.15 mol/L,8.0 mL/kg).4-{3-[6-Amino-9-(5-ethylcarbamoyl-3,4-dihydroxy-tetrahydro-furan-2-yl)-9H-purin-2-yl]-prop-2-ynyl}-cyclohexanecarboxylic acid methyl ester(ATL-146e,2.5-5 μg/kg,IP)was injected 30 min before the admin-istration of aspirin.Tissue myeloperoxidase(MPO)con-centration in gastric mucosa was measured as an indexof neutrophil infiltration.Gastric mucosal concentrationsof tumor necrosis factor-α(TNF-α)and interleukin-1β(IL-1β)were determined by ELISA.Also,we examinedthe effect of ATL-146e on tissue prostaglandin E2(PGE2)production and gastric secretion.RESULTS:Intragastric administration of aspirin inducedmultiple hemorrhagic erosions in rat gastric mucosa.Thetotal length of gastric erosions(ulcer index)in controlrats was 29.8±7.75 mm and was reduced to 3.8±1.42mm after pretreatment with 5.0 g/kg ATL-146e(P<0.01).The gastric contents of MPO and pro-inflammatory cy-tokines were all increased after the administration ofaspirin and reduced to nearly normal levels by ATL-146e.Gastric mucosal PGE2 concentration was not affected byintraperitoneal injection of ATL-146e.CONCLUSION:The specific adenosine A_(2A) receptor ago-nist,ATL-146e,has potent anti-ulcer effects presumablymediated by its anti-inflammatory properties. AIM: To determine whether a specific adenosine A_ (2A) re-ceptor agonist (ATL-146e) can ameliorate aspirin-induced gastric mucosal lesions in rats, and reduce neutrophil ac-cumulation and production of pro-inflammatory cytokines. METHODS: Gastric lesions were produced by oralgarage of aspirin (200 mg / kg) and HCl (0.15 mol / L, 8.0 mL / kg) .4- {3- [6-Amino-9- (5-ethylcarbamoyl- 2-yl] -prop-2-ynyl} -cyclohexanecarboxylic acid methyl ester (ATL-146e, 2.5-5 μg / kg, IP) was injected 30 min before the admin- istration of aspirin.Tissue myeloperoxidase (MPO) con-centration in gastric mucosa was measured as an index of neutrophil infiltration. Gastric mucosal concentrations of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL- , we examined the effect of ATL-146e on tissue prostaglandin E2 (PGE2) production and gastric secretion .RESULTS: Intragastric administration of aspirin induced multiple acute hemorrhagic erosions in rat gastric mucosa. h of gastric erosions (ulcer index) in controlrats was 29.8 ± 7.75 mm and was reduced to 3.8 ± 1.42 mm after pretreatment with 5.0 g / kg of ATL-146e (P <0.01). gastric contents of MPO and pro-inflammatory cy- tokines were all increased after the administration of aspirin and reduced to nearly normal levels by ATL-146e. Gastric mucosal PGE2 concentration was not affected by inperitoneal injection of ATL-146e. CONCLUSION: The specific adenosine A 2Ar receptor ago- , has potent anti-ulcer effects presumablymediated by its anti-inflammatory properties.
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